Human fetal liver, obtained as early as the eighth week of gestation, has been shown to have the capacity to catalyze the biotransformation of a number of drugs. Fetal livers from a number of common laboratory animals have been examined but none have exhibited this capacity. We have recently shown that the fetal liver from the nonhuman primate, Macaca arctoides, is capable, as early as midgestation, of catalyzing the oxidative N-demethylation of ethylmorphine. The fetal hepatic ultrastructure of this species appears quite similar to the human fetal liver at 12-16 weeks gestation. The objective of the proposed research is to study systemically the fetal liver from this nonhuman primate, with respect to ultranstructure and drug metabolizing capacity, and compare it with that of the human fetal liver. Drugs of abuse (barbiturates, codeine, meperidine, methadone) will be utilized as substrates. Studies will focus on the development of the oxidative drug metabolizing activity of the mixed function oxidase system of microsomal enzymes isolated from the livers of these two species. The biochemical findings will be correlated with ultrastructure. The aim is to evaluate the extent to which the development of drug metabolism in the liver of the fetal monkey is comparable to that of the human and to relate our findings, inasmuch as possible, to clinical medicine. The long term research objective is to develop the fetal nonhuman primate system into an animal model for the study of maternal-fetal drug interactions and their significance to the developing human fetus.